A reproducible large animal model without the disadvantages imposed by implantation of carcinogens or heterotransplants would enhance investigation of the biology and treatment of infiltrative, intrinsic glial tumors. Radiation has been implicated in the development of primary CNS tumors in humans and animal models. We describe the development of glioblastoma multiforme (GBM) in 5 of 11 rhesus monkeys 0.5-4.5 years after 35 Gy whole brain radiation.11 monkeys were treated with fractionated whole brain radiation (350 cGy/day x 10 d). We obtained non- and contrast-enhanced MRIs before treatment and serially after treatment. Animals were sacrificed when they developed neurological symptoms or parenchymal lesions on MRI. 4 animals are alive, three of whom are without MRI abnormalities. The other is currently developing a large lesion in the left fronto-parietal white matter and corpus callosum. 1 animal developed neurological symptoms 2.5 yrs after radiation but had no evidence of radiographic or microscopic disease. All animals that received radiation only developed GBMs, while 2/5 animals treated with pentobarbital and radiation developed GBMs.7 animals developed tumors which appeared as contrast-enhancing masses on MRI after 6 months (N=1), 2 y (N=2), and 4 y (N=2), 6.5 y (N=1) and 7y (N=1). 3 animals survived for 0.5, 2 and 3 yrs after development of MRI abnormalities. The lesions were supratentorial (N=5), infratentorial (N=2) and in both compartments (N=1). 3 animals had diffuse bilateral lesions. Six animals have histologically confirmed GBMs. 4 animals had multifocal tumors on histopathological analysis. All tumors demonstrated hypercellularity with giant cells, nuclear pleomorphism, mitoses, neovascularity, necrosis, and pseudopalisading. Extensive infiltration occurred along white matter tracts and along Virchow-Robin spaces. Work is in progress to investigate the pattern of expression of VEGF, transferrin receptor, and other markers of malignant gliomas.This infiltrative glioma model, which has histopathological characteristics identical to gliomas in humans, will be useful for investigation of the anatomy and mechanism of tumor infiltration, for genetic analysis of tumor progression, and for examining new treatments for infiltrative glial tumors